Correlation between ILC2 and Th17/Treg ratio in peripheral blood of patients at different stages of Mycobacterium tuberculosis infection / 中华微生物学和免疫学杂志

Objective:To study the correlation between type 2 innate lymphocyte (ILC2) and Treg/Th17 ratio in the peripheral blood of patients at different stages of Mycobacterium tuberculosis ( Mtb) infection. Methods:This study recruited 30 individuals with active tuberculosis (ATB group), 26 with treated tuberculosis (RTB group), 22 with latent tuberculosis infection (LTBI group) and 17 negative for tuberculin skin test (TST-negative group). Flow cytometry was used to detect the proportion of ILC2 in CD45 + cells, and that of Th17 and Treg cells in CD4 + T lymphocytes in the peripheral blood of patients in each group. Expression of Foxp3 and RORγt at mRNA level was detected by real-time fluorescence quantitative PCR. Pearson method was used to analyze the correlation between Th17 and Treg, and that between ILC2 and Treg/Th17 ratio in the peripheral blood of patients with ATB and RTB. Results:The proportions of ILC2 in RTB and ATB groups were significantly higher than those of LTBI and TST-negative groups, and the proportion of ILC2 in RTB group was significantly higher than that of ATB group ( P<0.05). The proportion of Th17 in RTB group was lower than that of ATB group ( P<0.05), and the proportions of Th17 in ATB and RTB groups were lower than those of LTBI and TST-negative groups. The proportion of Treg in RTB group was lower than that of ATB group ( P<0.05), and close to that of LTBI group and TST-negative group, but the Treg/Th17 ratios in ATB and RTB groups were higher than those of LTBI and TST-negative groups. There was no significant difference in Treg/Th17 ratio between ATB and RTB groups ( P>0.05). The expression of Foxp3 and RORγt at mRNA level and Foxp3/RORγt ratio changed accordingly. Meanwhile, there was no correlation between Th17 and Treg in ATB or RTB group ( r=0.023, P=0.444; r=0.428, P=0.150). There was a positive correlation between ILC2 and Treg/Th17 ratio in ATB group ( r=0.794, P=0.000), while no correlation was found between ILC2 and Treg/Th17 ratio in RTB group ( r=0.197, P=0.297). Conclusions:In this study, the proportion of ILC2 was increased in the peripheral blood of TB patients, and the proportion of ILC2 in RTB group was higher than that of ATB group. In RTB group, Th17 accounted for a low proportion in the peripheral blood and was involved in inflammatory reactions, while Tregs were not involved in inflammatory reactions, but might have a certain inhibitory effect in patients with ATB. Further studies found that Th17-involved inflammatory reactions were not regulated by Tregs. ILC2 was involved in Treg/Th17 imbalance in ATB patients, but not in RTB patients.

Allergen-Dependent Differences in ILC2s Frequencies in Patients With Allergic Rhinitis

PURPOSE: Group 2 innate lymphoid cells (ILC2s) are a novel population of lineage-negative cells that induce innate type 2 responses by producing the critical Th2-type cytokines IL-5 and IL-13 in response to IL-25 and IL-33 stimulation. ILC2s accumulation in the peripheral blood of patients with allergic rhinitis (AR) is controversial; the precise role of ILC2s in the immunopathogenesis of AR is still not clear. We investigated the role of ILC2s in phenotypic AR sensitized to distinct allergens. METHODS: Flow cytometric analysis of the peripheral blood of 7 healthy controls (HCs), 9 patients monosensitized to house dust mite (HDM), and 8 patients monosensitized to mugwort was performed to quantify ILC2s frequency. Peripheral blood mononuclear cells (PBMCs) were isolated from HDM-AR and mugwort-AR patients, and Lineage- and Lineage+ cells were separated using a fluorescence-activated cell sorter (FACS). IL-5 and IL-13 levels in the supernatants of PBMCs, and Lineage- and Lineage+ cells stimulated with IL-25 and/or IL-33 combined with IL-2 in vitro were assessed using the Milliplex magnetic bead kit. RESULTS: The percentage of ILC2s was significantly elevated in HDM-AR patients compared to mugwort-AR patients and HCs, while no significant difference was found between mugwort-AR patients and HCs. IL-33+/-IL-25 plus IL-2 induced a significantly greater release of IL-5 and IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. IL-25 plus IL-2 also induced a significantly greater release of IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. Stimulation with IL-33 and/or IL-25 combined with IL-2 also induced a significantly greater IL-5 and IL-13 release from Lineage- cells compared to Lineage+ cells. CONCLUSIONS: AR patients sensitized to HDM or mugwort allergen have distinct phenotypic and functional profiles in ILC2s frequencies. ILC2s mediate major type 2 immunity in the development of HDM-AR and may be a potential therapeutic target.

Regulation of IgE-Mediated Food Allergy by IL-9 Producing Mucosal Mast Cells and Type 2 Innate Lymphoid Cells

Due to the increasing prevalence and number of life-threatening cases, food allergy has emerged as a major health concern. The classic immune response seen during food allergy is allergen-specific IgE sensitization and hypersensitivity reactions to foods occur in the effector phase with often severe and deleterious outcomes. Recent research has advanced understanding of the immunological mechanisms occurring during the effector phase of allergic reactions to ingested food. Therefore, this review will not only cover the mucosal immune system of the gastrointestinal tract and the immunological mechanisms underlying IgE-mediated food allergy, but will also introduce cells recently identified to have a role in the hypersensitivity reaction to food allergens. These include IL-9 producing mucosal mast cells (MMC9s) and type 2 innate lymphoid cells (ILC2s). The involvement of these cell types in potentiating the type 2 immune response and developing the anaphylactic response to food allergens will be discussed. In addition, it has become apparent that there is a collaboration between these cells that contributes to an individual's susceptibility to IgE-mediated food allergy.

Research progress on type Ⅱ innate lymphoid cells in respiratory mucosal immunity and lung diseases / 中国免疫学杂志

Type Ⅱ innate lymphoid cells is an emerging family of innate lymphocytes mainly distributed in mucosal tissues such as the lungs,intestines,skin,etc.These cells are capable of producing Th2-type cytokines including IL-5 and IL-13 in response to IL-25 and IL-33.ILC2s has attracted much attention for its important roles in anti-infection immunity and allergic diseases in respiratory tract.Studies have shown that ILC2s represented a crucial source of Th2-type cytokines and could regulate the adaptive immune response in allergic airway diseases.Meanwhile,ILC2s was able to fulfill vital functions in parasite clearance, anti-virus infection and subsequent tissue repair.Therefore,research in ILC2s phenotype,development and function has great practical significance.This paper reviews the definition, classification, developmental regulation of ILC2s with a particular focus on its role in respiratory mucosal homeostasis and lung-related diseases.